Abstract 3617: Blockade of T-Type Calcium Channels Suppresses Cellular Synthesis and Plasma Levels of Aldosterone in Human
Aldosterone is importantly involved in the development and progression of cardiovascular and renal disease. Little has been reported on the effect of the blockade of T-type calcium channel on aldosterone secretion both in vitro and vivo.
Objective: The aim of this study was to evaluate the effect of Efonidipine (E: dominant T-type calcium channel blocker (TCCB)) on aldosterone synthesis from human adrenocortical tumor cell line (H295R) in vitro, and also to confirm the clinical effect of E on plasma levels of neurohumoral factors including aldosterone in healthy volunteers.
Methods and results: Aldosterone synthesis from AngII (100 nmol/L) or potassium (10 mmol/L) stimulated H295R cells were studied under co-incubation with the graded concentrations of E, Mibefradil (M: selective TCCB), or Nifedipine (Nf: dominant L-type CCB). Following 48h co-incubation, media was assayed for aldosterone and cortisol. Effects of these agents on the gene expression of CYP11B2, a gene encoding aldosterone synthase, were also studied. AngII stimulated the aldosterone secretion up to 12-fold higher than basal level. IC50 value of E (0.441 ± 0.067 μmol/L) was significantly smaller than those of Nf and M (3.36 ± 0.49 μmol/L and 1.08 ± 0.10 μmol/L, respectively), so E was found to be the most efficient antagonist. Cortisol secretion was also repressed by E. Gene expression of CYP11B2, a gene encoding aldosterone synthase, was significantly depressed by E. Five healthy male volunteers were recruited in this study. Subjects were given a single dose of placebo, 40mg of E, or 2mg of Nilvadipine (Nl: dominant LCCB), and quietly stayed on bed for 6 hours. Hemodynamic parameters (pulse rate and blood pressure) and plasma levels of neurohormonal factors were measured before and 6 hours after administration. E and Nl significantly increased plasma levels of active renin and AngII. Plasma levels of aldosterone significantly decreased after E treatment (88.3 ± 21.3 to 81.6 ± 24.9 pg/ml), while significantly increased after Nl treatment (66.5±12.2 to 82.17±16.6 pg/ml). Placebo did not change plasma levels of active renin, AngII, and aldosterone.
Conclusion: Efonidipine suppressed both cellular synthesis and the elevation plasma aldosterone levels by angiotensin II stimulation.